Biguanide-functionalized peptide mimics effectively combat drug-resistant ESKAPE pathogens and meningitis.

ABSTRACT: ESKAPE pathogens-induced meningitis seriously threatens human health due to antimicrobial resistance and low permeability of blood-brain barrier (BBB). It's a promising strategy to combat drug-resistant pathogens using synthetic mimics of host defense peptide (HDP) bearing positive charges that are mainly provided by amine or guanidine. Here, we report that biguanide serves as a type of positively charged moiety to design HDP mimics. Biguanide exerts a stronger interaction with bacterial membrane phospholipids via bidentate hydrogen bonds than do amine and guanidine. The biguanide-functionalized HDP mimic, PBGProOx₂₀, targets bacterial membrane phospholipids to show potent activity against all ESKAPE pathogens and does not induce antimicrobial resistance. PBGProOx₂₀ e

SUBMITTER: Jiang W 

PROVIDER: S-EPMC12789443 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature